U.S. patent application number 12/058387 was filed with the patent office on 2009-08-13 for novel salts and their uses.
This patent application is currently assigned to COLGATE-PALMOLIVE COMPANY. Invention is credited to Virginia Monsul Barnes, Suman Chopra, Diane Cummins, Rajnish Kohli, Sergio Leite, Sarita V. Mello, Andre M. Morgan, Michael Prencipe, Richard Scott Robinson, Ralph Peter Santarpia, III, Eric A. Simon, Ravi Subramanyam, Richard J. Sullivan, Gary Edward Tambs, Qin Wang, Donghui Wu, Guofeng Xu, Lynette Zaidel.
Application Number | 20090202456 12/058387 |
Document ID | / |
Family ID | 40020250 |
Filed Date | 2009-08-13 |
United States Patent
Application |
20090202456 |
Kind Code |
A1 |
Prencipe; Michael ; et
al. |
August 13, 2009 |
NOVEL SALTS AND THEIR USES
Abstract
The invention relates to novel arginine salts, compositions
comprising them, and their uses.
Inventors: |
Prencipe; Michael; (West
Windsor, NJ) ; Xu; Guofeng; (Plainsboro, NJ) ;
Subramanyam; Ravi; (Belle Mead, NJ) ; Wu;
Donghui; (Bridgewater, NJ) ; Cummins; Diane;
(Livingston, NJ) ; Sullivan; Richard J.; (Atlantic
Highlands, NJ) ; Santarpia, III; Ralph Peter;
(Edison, NJ) ; Mello; Sarita V.; (Somerset,
NJ) ; Zaidel; Lynette; (Cranford, NJ) ;
Chopra; Suman; (Monroe, NJ) ; Wang; Qin;
(Monmouth Junction, NJ) ; Tambs; Gary Edward;
(Belle Mead, NJ) ; Barnes; Virginia Monsul;
(Ringoes, NJ) ; Morgan; Andre M.; (Robbinsville,
NJ) ; Kohli; Rajnish; (Hillsborough, NJ) ;
Robinson; Richard Scott; (Belle Mead, NJ) ; Leite;
Sergio; (Kendall Park, NJ) ; Simon; Eric A.;
(Somerset, NJ) |
Correspondence
Address: |
COLGATE-PALMOLIVE COMPANY
909 RIVER ROAD
PISCATAWAY
NJ
08855
US
|
Assignee: |
COLGATE-PALMOLIVE COMPANY
New York
NY
|
Family ID: |
40020250 |
Appl. No.: |
12/058387 |
Filed: |
March 28, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61027442 |
Feb 9, 2008 |
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61027432 |
Feb 8, 2008 |
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61027431 |
Feb 8, 2008 |
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61027420 |
Feb 8, 2008 |
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Current U.S.
Class: |
424/54 ;
514/565 |
Current CPC
Class: |
A61K 8/44 20130101; A61K
8/463 20130101; A61P 31/02 20180101; A61P 1/02 20180101; A61K
8/8164 20130101; A61K 8/55 20130101; A61K 31/198 20130101; A61Q
11/00 20130101 |
Class at
Publication: |
424/54 ;
514/565 |
International
Class: |
A61K 8/44 20060101
A61K008/44; A61K 31/195 20060101 A61K031/195; A61Q 11/00 20060101
A61Q011/00 |
Claims
1. A salt of arginine and one or more of the following conjugate
acids: a. an acidic polymer; b. a conjugate acid of an anionic
surfactant salt; c. a polyphosphoric or polyphosphonic acid, or d.
an acidic antimicrobial agent.
2. The salt of claim 1 in solid form.
3. The salt of claim 1, wherein the conjugate acid is an acidic
polymer.
4. The salt of claim 1, wherein the conjugate acid is the conjugate
acid of an anionic surfactant salt.
5. The salt of claim 1, wherein the conjugate acid is a
polyphosphoric acid.
6. The salt of claim 1, wherein conjugate acid is a polyphosphonic
acid.
7. The salt of claim 1, wherein the conjugate acid is an acidic
antimicrobial agent.
8. The salt of claim 3, wherein the acidic polymer is a
polycarboxylate polymer.
9. The salt of claim 8 wherein the polycarboxylate polymer is a
copolymer of methyl vinyl ether and maleic anhydride.
10. The salt of claim 4, wherein the acid is lauroyl sulfuric
acid.
11. The salt of claim 5, wherein the polyphosphoric acid is
hexametaphosphoric acid.
12. The salt of claim 7 wherein the acid is a benzoic acid
optionally substituted with carboxy and one or more hydroxys.
13. The salt of claim 12, wherein the acidic antimicrobial agent is
gallic acid.
14. An oral care composition comprising the salt of claim 1.
15. A method comprising applying an effective amount of the salt of
claim 1 or the composition of claim 14 to the oral cavity of a
subject in need thereof to i. reduce or inhibit formation of dental
caries, ii. reduce, repair or inhibit early enamel lesions, iii.
reduce or inhibit demineralization and promote remineralization of
the teeth, iv. reduce hypersensitivity of the teeth, v. reduce or
inhibit gingivitis, vi. promote healing of sores or cuts in the
mouth, vii. reduce levels of acid producing bacteria, viii. to
increase relative levels of arginolytic bacteria, ix. inhibit
microbial biofilm formation in the oral cavity, x. raise and/or
maintain plaque pH at levels of at least pH about 5.5 following
sugar challenge, xi. reduce plaque accumulation. xii. treat,
relieve or reduce dry mouth, xiii. whiten teeth, xiv. enhance
systemic health, including cardiovascular health, xv. reduce
erosion of the teeth, xvi. immunize the teeth against cariogenic
bacteria, and/or xvii. clean the teeth and oral cavity.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Ser. No.
61/027,442 filed Feb. 9, 2008, U.S. Ser. No. 61/027,432 filed Feb.
8, 2008. U.S. Ser. No. 61/027,431 filed Feb. 8, 2008 and U.S. Ser.
No. 61/027,420 filed Feb. 8, 2008, the contents of which
applications are incorporated herein by reference.
FIELD OF THE INVENTION
[0002] This invention relates to novel salts of arginine and
compositions comprising them.
BACKGROUND OF THE INVENTION
[0003] Arginine and other basic amino acids have been proposed for
use in oral care and are believed to have significant benefits in
combating cavity, formation and tooth sensitivity. Combining these
basic amino acids with minerals having oral care benefits, e.g.,
fluoride and calcium, to form an oral care product having
acceptable long term stability, however, has proven challenging. In
particular, the basic amino acid may raise the pH and facilitate
dissociation of calcium ions that can react with fluoride ions to
form an insoluble precipitate. Moreover, the higher pH has the
potential to cause irritation. At neutral pH or acidic pH, however,
a system utilizing arginine bicarbonate (which the art teaches is
preferred) may release carbon dioxide, leading to bloating and
bursting of the containers. Moreover, it might be expected that
lowering the pH to neutral or acidic conditions would reduce the
efficacy of the formulation because the arginine may form an
insoluble arginine-calcium complex that has a poorer affinity for
the tooth surface, and moreover that lowering the pH would reduce
any effect the formulation might have on buffering cariogenic
lactic acid in the mouth. Partly because of these unaddressed
formulation hurdles and partly because arginine has generally been
viewed in the art as a potential alternative to fluoride rather
than a co-active, there has been little motivation to make oral
care products comprising both arginine and fluoride. Additional
hurdles are potentially posed by addition of an antimicrobial
agent. Commercially available arginine-based toothpaste, such as
ProClude.RTM. and DenClude.RTM., for example, contain arginine
bicarbonate and calcium carbonate, but not fluoride nor any
antimicrobial agent.
[0004] At the same time, the value of antimicrobial agents, such as
triclosan, in toothpaste has been recognized by many dentists.
These agents however are challenging to deliver in effective
amounts to the teeth and gums, and their solubility, delivery and
retention on the teeth is formulation dependent. For example,
triclosan(5-chloro-2-(2,4-dichlorophenoxy)phenol) is only slightly
soluble in water.
[0005] Accordingly, there is a need for a stable oral care product
providing arginine, as well as improved delivery of beneficial
minerals such as fluoride and calcium, and of poorly soluble active
agents.
SUMMARY OF THE INVENTION
[0006] It has been surprisingly discovered that these problems can
be addressed using functional salts of arginine.
[0007] The invention thus provides in one embodiment a salt of
arginine and one or more of the following cations [0008] i. an
acidic polymer, e.g., a polycarboxylate polymer; [0009] ii. the
conjugate acid of an anionic surfactant, e.g., lauroyl sulfuric
acid; [0010] iii. a polyphosphoric or polyphosphonic acid, e.g.,
hexametaphosphoric acid; or [0011] iv. an acidic antimicrobial
agent, e.g., gallic acid.
[0012] In other embodiments, the invention provides oral and
personal care products comprising the salts of the invention, and
methods of making and using the salts and products.
[0013] The salt can be used in compositions to promote oral health
and/or systemic health, including cardiovascular health, e.g., by
reducing potential for systemic infection via the oral tissues.
DETAILED DESCRIPTION
[0014] In a first embodiment (Salt 1.0), the invention provides a
salt of arginine and an acidic polymer, e.g., a polymeric
polycarboxylate, for example, [0015] 1.0.1. Salt 1.0 wherein the
polymeric polycarboxylate is a 1:4 to 4:1 copolymer of maleic
anhydride or acid with another polymerizable ethylenically
unsaturated monomer. [0016] 1.0.2. Salt 1.0.1 wherein the
polycarboxylate comprises units formed of maleic anhydride and
methyl vinyl ether, e.g., depicted at pH 7 as follows:
[0016] ##STR00001## [0017] 1.0.3. Salt 1.0.2 wherein the methyl
vinyl ether/maleic anhydride has a molecular weight (M.W.) of about
30,000 to about 1,000,000. [0018] 1.0.4. Salt 1.0.3 wherein the
methyl vinyl ether/maleic anhydride has a molecular weight (M.W.)
of about 700,000.
[0019] In another embodiment, the invention provides a salt of
arginine and the conjugate acid of an anionic surfactant salt (Salt
2.0). For example the invention provides salts as follows: [0020]
2.0.1. Salt 2.0 wherein the conjugate acid is of an anionic
surfactant salt is selected from [0021] a. water-soluble salts of
higher fatty acid monoglyceride monosulfate (e.g., salt of the
monosulfated monoglyceride of hydrogenated coconut oil fatty acids
such as sodium N-methyl N-cocoyl taurate, sodium cocomo-glyceride
sulfate), [0022] b. higher alkyl sulfates, e.g., sodium lauryl
sulfate, [0023] c. higher alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.3H,
wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na
or K (for example sodium laureth-2 sulfate
(CH.sub.3(CH.sub.2).sub.10(CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na))-
, [0024] d. higher alkyl aryl sulfonates (such as sodium dodecyl
benzene sulfonate (sodium lauryl benzene sulfonate)), [0025] e.
higher alkyl sulfoacetates (such as sodium lauryl sulfoacetate
(dodecyl sodium sulfoacetate), higher fatty acid esters of 1,2
dihydroxy propane sulfonate. sulfocolaurate (N-2-ethyl laurate
potassium sulfoacetamide) and sodium lauryl sarcosinate), [0026] f.
and mixtures thereof, [0027] e.g., wherein by "higher alkyl" is
meant C.sub.6-30 alkyl, for example C.sub.8-18. [0028] 2.0.2. Salt
2.0 or 2.0.1 which is a salt of arginine and lauroyl sulfuric
acid.
[0029] In another embodiment, the invention provides arginine
polyphosphate or polyphosphonate salts (Salt 3.0), for example:
[0030] 3.0.1. Salt 3.0 when a salt of arginine and polyvinyl
phosphonic acid. [0031] 3.0.2. Salt 3.0 when a salt of arginine and
a polyphosphoric acid. [0032] 3.0.3. Salt 3.0 when a salt of
arginine and hexametaphosphoric acid. [0033] 3.0.4. Salt 3.0 when a
salt of arginine and pyrophosphoric acid. [0034] 3.0.5. Salt 3.0
when a salt of arginine and a tripolyphosphate salt.
[0035] In another embodiment, the invention provides salts of
arginine and an antibacterial acid (Salt 4.0). In a particular
embodiment (Salt 4.0.1), the invention provides salts of arginine
and a benzoic acid optionally substituted with carboxy and/or one
or more, e.g., 1, 2, or 3 hydroxys, e.g., benzoic acid, phthalic
acid, salicylic acid or trihydroxybenzoic acid, for example, gallic
acid.
[0036] The invention further provides an oral care composition
(Composition 1.1) comprising any of Salts 1.0-1.0.4; 2.0-2.0.2,
3.0-3.0.5 or 4.0-4.0. 1. e.g., [0037] 1.1.1. Composition 1.1
further comprising an antibacterial agent. The antibacterial agent
may be selected from halogenated diphenyl ether (e.g. triclosan),
herbal extracts and essential oils (e.g., rosemary extract, tea
extract, magnolia extract, thymol, menthol, eucalyptol, geraniol,
carvacrol, citral, hinokitol, catechol, methyl salicylate,
epigallocatechin gallate, epigallocatechin, gallic acid, miswak
extract, sea-buckthorn extract), bisguanide antiseptics (e.g.,
chlorhexidine, alexidine or octenidine), quaternary ammonium
compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium
chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic
antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, metal ions (e.g., zinc salts, for example,
zinc citrate, stannous salts, copper salts, iron salts),
sanguinarine propolis and oxygenating agents (e.g., hydrogen
peroxide, buffered sodium peroxyborate or peroxycarbonate),
phthalic acid and its salts, monoperthalic acid and its salts and
esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl
sulfosuccinate, salicylanilide, domiphen bromide, delmopinol,
octapinol and other piperidino derivatives, nicin preparations,
chlorite salts; and mixtures of any of the foregoing. [0038] 1.1.2.
Composition 1.1.1 wherein the antibacterial agent is triclosan.
[0039] 1.1.3. Any of the preceding composition comprising triclosan
and Zn.sup.2+ ion source, e.g., zinc citrate. [0040] 1.1.4. Any of
the preceding compositions further comprising an anti-calculus
agent. [0041] 1.1.5. Any of the preceding compositions further
comprising an anti-calculus agent which is a polyphosphate, e.g.,
pyrophosphate, tripolyphosphate, or hexametaphosphate, e.g., in
sodium salt form. [0042] 1.1.6. Any of the foregoing Compositions
further comprising a fluoride ion source. [0043] 1.1.7. Composition
1.1.6 wherein the fluoride ion source is a soluble fluoride salt
selected from stannous fluoride, sodium fluoride, potassium
fluoride, sodium monofluorophosphate, sodium fluorosilicate,
ammonium fluorosilicate, amine fluoride (e.g.,
N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride),
ammonium fluoride, titanium fluoride, hexafluorosulfate, and
combinations thereof. [0044] 1.1.8. Any of the foregoing
Compositions further comprising a surfactant. [0045] 1.1.9. Any of
the compositions further comprising an agent that interferes with
or prevents bacterial attachment, e.g., solbrol or chitosan. [0046]
1.1.10. Any of the foregoing Compositions in the form of a
toothpaste optionally further comprising one or more of one or more
of water, abrasives, surfactants, foaming agents, vitamins,
polymers, enzymes, humectants, thickeners, antimicrobial agents,
preservatives, flavorings, colorings and/or combinations
thereof.
[0047] The invention further comprises a method to improve oral
health comprising applying an effective amount of any of Salts
1.0-1.0.4; 2.0-2.0.2, 3.0-3.0.5 or 4.0-4.0.1, or any of
Compositions 1.1-1.1.9 to the oral cavity of a subject in need
thereof to [0048] i. reduce or inhibit formation of dental caries,
[0049] ii. reduce, repair or inhibit early enamel lesions, [0050]
iii. reduce or inhibit demineralization and promote
remineralization of the teeth, [0051] iv. reduce hypersensitivity
of the teeth, [0052] v. reduce or inhibit gingivitis, [0053] vi.
promote healing of sores or cuts in the mouth, [0054] vii. reduce
levels of acid producing bacteria, [0055] viii. to increase
relative levels of arginolytic bacteria, [0056] ix. inhibit
microbial biofilm formation in the oral cavity, [0057] x. raise
and/or maintain plaque pH at levels of at least pH about 5.5
following sugar challenge, [0058] xi. reduce plaque accumulation.
[0059] xii. treat, relieve or reduce dry mouth, [0060] xiii. whiten
teeth, [0061] xiv. enhance systemic health, including
cardiovascular health, e.g., by reducing potential for systemic
infection via the oral tissues, [0062] xv. reduce erosion of the
teeth, [0063] xvi. immunize the teeth against cariogenic bacteria,
and/or [0064] xvii. clean the teeth and oral cavity. The invention
further provides the use of any of Salts 1.0-1.0.4; 2.0-2.0.2,
3.0-3.0.5 or 4.0-401, or any of Compositions 1.1-1.1.9, for any of
the above-listed indications.
[0065] In various embodiments of the Compositions of the invention,
the basic amino acid is present in an amount of about 0.5 wt. % to
about 20 wt. % of the total composition weight, about 1 wt. % to
about 10 wt. % of the total composition weight, for example about
1.5 wt. %, 3.75 wt. %, 5 wt. %, or 7.5 wt. % of the total
composition weight.
Fluoride Ion Source
[0066] The oral care compositions may further include one or more
fluoride ion sources, e.g., soluble fluoride salts. A wide variety
of fluoride ion-yielding materials can be employed as sources of
soluble fluoride in the present compositions. Examples of suitable
fluoride ion-yielding materials are found in U.S. Pat. No.
3,535,421, to Briner et al.: U.S. Pat. No. 4,885,155, to Parran,
Jr. et al. and U.S. Pat. No. 3.678,154, to Widder et al.,
incorporated herein by reference.
[0067] Representative fluoride ion sources include, but are not
limited to, stannous fluoride, sodium fluoride, potassium fluoride,
sodium monofluorophosphate, sodium fluorosilicate, ammonium
fluorosilicate, amine fluoride, ammonium fluoride, and combinations
thereof. In certain embodiments the fluoride ion source includes
stannous fluoride, sodium fluoride, sodium monofluorophosphate as
well as mixtures thereof.
[0068] In certain embodiments the oral care composition of the
invention may also contain a source of fluoride ions or
fluorine-providing ingredient in amounts sufficient to supply about
25 ppm to about 25,000 ppm of fluoride ions, generally at least
about 500 ppm, e.g., 500 to about 2000 ppm, e.g., about 1000 to
about 1600 ppm, e.g., about 1450 ppm. The appropriate level of
fluoride will depend on the particular application. A mouthwash,
for example, would typically have about 100 to about 250 ppm
fluoride. A toothpaste for general consumer use would typically
have about 1000 to about 1500 ppm, with pediatric toothpaste having
somewhat less. A dentifrice or coating for professional application
could have as much as about 5,000 or even about 25,000 ppm
fluoride.
[0069] Fluoride ion sources may be added to the compositions of the
invention at a level of about 0.01 wt. % to about 10 wt. % in one
embodiment or about 0.03 vat. % to about 5 wt. %, and in another
embodiment about 0.1 wt. % to about 1 wt. % by weight of the
composition in another embodiment. Weights of fluoride salts to
provide the appropriate level of fluoride ion will obviously vary
based on the weight of the counter ion in the salt.
Abrasives
[0070] The Compositions of the Invention may comprise a calcium
phosphate abrasive, e.g., tricalcium phosphate
(Ca.sub.3(PO.sub.4).sub.2), hydroxyapatite
(Ca.sub.10(PO.sub.4).sub.6(OH).sub.2), or dicalcium phosphate
dihydrate (CaHPO.sub.4.2H.sub.2O, also sometimes referred to herein
as DiCal) or calcium pyrophosphate.
[0071] The compositions may include one or more additional
abrasives, for example silica abrasives such as precipitated
silicas having a mean particle size of up to about 20 microns, such
as Zeodent 115.RTM., marketed by J. M. Huber. Other useful
abrasives also include sodium metaphosphate, potassium
metaphosphate, aluminum silicate, calcined alumina, bentonite or
other siliceous materials, or combinations thereof.
[0072] The silica abrasive polishing materials useful herein, as
well as the other abrasives, generally have an average particle
size of about 0.1 to about 30 microns, about 5 to about 15 microns.
The silica abrasives can be from precipitated silica or silica
gels, such as the silica xerogels described in U.S. Pat. No.
3,538,230, to Pader et al. and U.S. Pat. No. 3,862,307, to
Digiulio, both incorporated herein by reference. Particular silica
xerogels are marketed under the trade name Syloid.RTM. by the W. R.
Grace & Co., Davison Chemical Division. The precipitated silica
materials include those marketed by the J. M. Huber Corp. under the
trade name Zeodent.RTM., including the silica carrying the
designation Zeodent 115 and 119. These silica abrasives are
described in U.S. Pat. No. 4,340,583, to Wason, incorporated herein
by reference.
[0073] In certain embodiments, abrasive materials useful in the
practice of the oral care compositions in accordance with the
invention include silica gels and precipitated amorphous silica
having an oil absorption value of about less than 100 cc/100 g
silica or about 45 cc/100 g to about 70 cc/100 g silica. Oil
absorption values are measured using the ASTM Rub-Out Method D281.
In certain embodiments, the silicas are colloidal particles having
an average particle size of about 3 microns to about 12 microns,
and about 5 to about 10 microns.
[0074] In particular embodiments, the abrasive materials comprise a
large fraction of very small particles, e.g., having a d50 less
than about 5 microns, for example, small particle silica (SPS)
having a d50 of 3-4 microns, for example Sorbosil AC43.RTM.
(Ineos). Such small particles are particularly useful in
formulations targeted at reducing hypersensitivity. The small
particle component may be present in combination with a second
larger particle abrasive. In certain embodiments, for example, the
formulation comprises about 3 to about 8% SPS and about 25 to about
45% of a conventional abrasive.
[0075] Low oil absorption silica abrasives particularly useful in
the practice of the invention are marketed under the trade
designation Sylodent XWA.RTM. by Davison Chemical Division of W.R.
Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA.RTM., a
silica hydrogel composed of particles of colloidal silica having a
water content of 29% by weight averaging about 7 to about 10
microns in diameter, and an oil absorption of less than about 70
cc/100 g of silica is an example of a low oil absorption silica
abrasive useful in the practice of the present invention. The
abrasive is present in the oral care composition of the present
invention at a concentration of about 10 to 60% by weight, in other
embodiment about 20 to 45% by weight, and in another embodiment
about 30 to 50% by weight.
Agents to Increase the Amount of Foaming
[0076] The oral care compositions of the invention also may include
an agent to increase the amount of foam that is produced when the
oral cavity is brushed.
[0077] Illustrative examples of agents that increase the amount of
foam include, but are not limited to polyoxyethylene and certain
polymers including, but not limited to, alginate polymers.
[0078] The polyoxyethylene may increase the amount of foam and the
thickness of the foam generated by the oral care carrier component
of the present invention. Polyoxyethylene is also commonly known as
polyethylene glycol ("PEG") or polyethylene oxide. The
polyoxyethylenes suitable for this invention will have a molecular
weight of about 200,000 to about 7,000,000. In one embodiment the
molecular weight will be about 600,000 to about 2,000,000 and in
another embodiment about 800,000 to about 1,000,000. Polyox.RTM. is
the trade name for the high molecular weight polyoxyethylene
produced by Union Carbide.
[0079] The polyoxyethylene may be present in an amount of about 1%
to about 90%, in one embodiment about 5% to about 50% and in
another embodiment about 10% to about 20% by weight of the oral
care carrier component of the oral care compositions of the present
invention. The dosage of foaming agent in the oral care composition
(i.e., a single dose) is about 0.01 to about 0.9% by weight, about
0.05 to about 0.5% by weight, and in another embodiment about 0.1
to about 0.2% by weight.
Surfactants
[0080] Another agent optionally included in the oral care
composition of the invention is a surfactant or a mixture of
compatible surfactants. Suitable surfactants are those which are
reasonably stable throughout a wide pH range, for example, anionic,
cationic, nonionic or zwitterionic surfactants.
[0081] Suitable surfactants are described more fully, for example,
in U.S. Pat. No. 3,959,458, to Agricola et al.; U.S. Pat. No.
3,937,807, to Haefele; and U.S. Pat. No. 4,051.234. to Gieske et
al., which are incorporated herein by reference.
[0082] In certain embodiments, the anionic surfactants useful
herein include the water-soluble salts of alkyl sulfates having
about 10 to about 18 carbon atoms in the alkyl radical and the
water-soluble salts of sulfonated monoglycerides of fatty acids
having about 10 to about 18 carbon atoms. Sodium lauryl sulfate,
sodium lauroyl sarcosinate and sodium coconut monoglyceride
sulfonates are examples of anionic surfactants of this type.
Mixtures of anionic surfactants may also be utilized.
[0083] In another embodiment, cationic surfactants useful in the
present invention can be broadly defined as derivatives of
aliphatic quaternary ammonium compounds having one long alkyl chain
containing about 8 to about 18 carbon atoms such as lauryl
trimethylammonium chloride, cetyl pyridinium chloride, cetyl
trimethylammonium bromide,
di-isobutylphenoxyethyldimethylbenzylammonium chloride, coconut
alkyltrimethylammonium nitrite, cetyl pyridinium fluoride, and
mixtures thereof.
[0084] Illustrative cationic surfactants are the quaternary
ammonium fluorides described in U.S. Pat. No. 3,535,421, to Briner
et al., herein incorporated by reference. Certain cationic
surfactants can also act as germicides in the compositions.
[0085] Illustrative nonionic surfactants that can be used in the
compositions of the invention can be broadly defined as compounds
produced by the condensation of alkylene oxide groups (hydrophilic
in nature) with an organic hydrophobic compound which may be
aliphatic or alkylaromatic in nature. Examples of suitable nonionic
surfactants include, but are not limited to, the Pluronics,
polyethylene oxide condensates of alkyl phenols, products derived
from the condensation of ethylene oxide with the reaction product
of propylene oxide and ethylene diamine, ethylene oxide condensates
of aliphatic alcohols, long chain tertiary amine oxides, long chain
tertiary phosphine oxides, long chain dialkyl sulfoxides and
mixtures of such materials.
[0086] In certain embodiments, zwitterionic synthetic surfactants
useful in the present invention can be broadly described as
derivatives of aliphatic quaternary ammonium, phosphomium, and
sulfonium compounds, in which the aliphatic radicals can be
straight chain or branched, and wherein one of the aliphatic
substituents contains about 8 to about 18 carbon atoms and one
contains an anionic water-solubilizing group, e.g., carboxy,
sulfonate, sulfate, phosphate or phosphonate. Illustrative examples
of the surfactants suited for inclusion into the composition
include, but are not limited to, sodium alkyl sulfate, sodium
lauroyl sarcosinate, cocoamidopropyl betaine and polysorbate 20,
and combinations thereof.
[0087] In a particular embodiment, the Composition of the Invention
comprises an anionic surfactant, e.g., sodium lauryl sulfate.
[0088] The surfactant or mixtures of compatible surfactants can be
present in the compositions of the present invention in about 0.1%
to about 5.0%, in another embodiment about 0.3% to about 3.0% and
in another embodiment about 0.5% to about 2.0% by weight of the
total composition.
Flavoring Agents
[0089] The oral care compositions of the invention may also include
a flavoring agent. Flavoring agents which are used in the practice
of the present invention include, but are not limited to, essential
oils as well as various flavoring aldehydes, esters, alcohols, and
similar materials. Examples of the essential oils include oils of
spearmint, peppermint, wintergreen, sassafras, clove, sage,
eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and
orange. Also useful are such chemicals as menthol, carvone, and
anethole. Certain embodiments employ the oils of peppermint and
spearmint.
[0090] The flavoring agent is incorporated in the oral composition
at a concentration of about 0.1 to about 5% by weight and about 0.5
to about 1.5% by weight. The dosage of flavoring agent in the
individual oral care composition dosage (i.e., a single dose) is
about 0.001 to 0.05% by weight and in another embodiment about
0.005 to 0.015% by weight.
Chelating Agents
[0091] The oral care compositions of the invention also may
optionally include one or more chelating agents able to complex
calcium found in the cell walls of the bacteria. Binding of this
calcium weakens the bacterial cell wall and augments bacterial
lysis.
[0092] Another group of agents suitable for use as chelating agents
in the present invention are the soluble pyrophosphates. The
pyrophosphate salts used in the present compositions can be any of
the alkali metal pyrophosphate salts. In certain embodiments, salts
include tetra alkali metal pyrophosphate, dialkali metal diacid
pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures
thereof, wherein the alkali metals are sodium or potassium. The
salts are useful in both their hydrated and unhydrated forms. An
effective amount of pyrophosphate salt useful in the present
composition is generally enough to provide at least 1.0 wt. %
pyrophosphate ions, about 1.5 wt. % to about 6 wt. %, about 3.5 wt.
% to about 6 wt. % of such ions.
Polymers
[0093] The oral care compositions of the invention also optionally
include one or more polymers, such as polyethylene glycols,
polyvinylmethyl ether maleic acid copolymers, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
or polysaccharide gums, for example xanthan gum or carrageenan
gum). Acidic polymers, for example polyacrylate gels, may be
provided in the form of their free acids or partially or fully
neutralized water soluble alkali metal (e.g., potassium and sodium)
or ammonium salts.
[0094] Particularly when noncationic antibacterial agents or
antibacterial agents, e.g., triclosan, are included in any of the
dentifrice components, there is also preferably included from about
0.05 to about 5% of an agent which enhances the delivery and
retention of the agents to, and retention thereof on oral surfaces.
Such agents useful in the present invention are disclosed in U.S.
Pat. Nos. 5,188,821 and 5,192,531; and include synthetic anionic
polymeric polycarboxylates, such as 1:4 to 4:1 copolymers of maleic
anhydride or acid with another polymerizable ethylenically
unsaturated monomer, preferably methyl vinyl ether/maleic anhydride
having a molecular weight (M.W.) of about 30,000 to about
1,000,000, most preferably about 30,000 to about 800,000. These
copolymers are available for example as Gantrez. e.g., AN 139 (M.W.
500,000), AN 119 (M.W. 250,000) and preferably S-97 Pharmaceutical
Grade (M.W. 700,000) available from ISP Technologies, Inc., Bound
Brook, N.J. 08805. The enhancing agents when present are present in
amounts of about 0.05 to about 3% by weight.
[0095] Other operative polymers include those such as the 1:1
copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl
methacrylate. N-vinyl-2-pyrollidone, or ethylene, the latter being
available for example as Monsanto EMA No. 1103, M.W. 10,000 and EMA
Grade 61, and 1:1 copolymers of acrylic acid with methyl or
hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl
ether or N-vinyl-2-pyrrolidone.
[0096] Suitable generally, are polymerized olefinically or
ethylenically unsaturated carboxylic acids containing an activated
carbon-to-carbon olefinic double bond and at least one carboxyl
group, that is, an acid containing an olefinic double bond which
readily functions in polymerization because of its presence in the
monomer molecule either in the alpha-beta position with respect to
a carboxyl group or as part of a terminal methylene grouping.
Illustrative of such acids are acrylic, methacrylic, ethacrylic,
alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic,
2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic acids and anhydrides. Other different olefinic monomers
copolymerizable with such carboxylic monomers include vinylacetate,
vinyl chloride, dimethyl maleate and the like. Copolymers contain
sufficient carboxylic salt groups for water-solubility.
[0097] A further class of polymeric agents includes a composition
containing homopolymers of substituted acrylamides and/or
homopolymers of unsaturated sulfonic acids and salts thereof in
particular where polymers are based on unsaturated sulfonic acids
selected from acrylamidoalykane sulfonic acids such as 2-acrylamide
2 methylpropane sulfonic acid having a molecular weight of about
1,000 to about 2,000,000, described in U.S. Pat. No. 4,842,847,
Jun. 27, 1989 to Zahid, incorporated herein by reference.
[0098] Another useful class of polymeric agents includes polyamino
acids, particularly those containing proportions of anionic
surface-active amino acids such as aspartic acid, glutamic acid and
phosphoserine, as disclosed in U.S. Pat. No. 4,866,161 Sikes et
al., incorporated herein by reference.
[0099] In preparing oral care compositions, it is sometimes
necessary to add some thickening material to provide a desirable
consistency or to stabilize or enhance the performance of the
formulation. In certain embodiments, the thickening agents are
carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and
water soluble salts of cellulose ethers such as sodium
carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl
cellulose. Natural gums such as karaya, gum arabic, and gum
tragacanth can also be incorporated. Colloidal magnesium aluminum
silicate or finely divided silica can be used as component of the
thickening composition to further improve the composition's
texture. In certain embodiments, thickening agents in an amount of
about 0.5% to about 5.0% by weight of the total composition are
used.
Enzymes
[0100] The oral care compositions of the invention may also
optionally include one or more enzymes. Useful enzymes include any
of the available proteases, glucanohydrolases, endoglycosidases,
amylases, mutanases, lipases and mucinases or compatible mixtures
thereof. In certain embodiments, the enzyme is a protease,
dextranase, endoglycosidase and mutanase. In another embodiment,
the enzyme is papain, endoglycosidase or a mixture of dextranase
and mutanase. Additional enzymes suitable for use in the present
invention are disclosed in U.S. Pat. No. 5,000,939 to Dring et al.,
U.S. Pat. No. 4,992,420; U.S. Pat. No. 4,355,022; U.S. Pat. No.
4,154,815; U.S. Pat. No. 4,058,595; U.S. Pat. No. 3,991,177; and
U.S. Pat. No. 3,696,191 all incorporated herein by reference. An
enzyme of a mixture of several compatible enzymes in the current
invention constitutes about 0.002% to about 2.0% in one embodiment
or about 0.05% to about 1.5% in another embodiment or in yet
another embodiment about 0.1% to about 0.5%.
Water
[0101] Water may also be present in the oral compositions of the
invention. Water, employed in the preparation of commercial oral
compositions should be deionized and free of organic impurities.
Water commonly makes up the balance of the compositions and
includes about 10% to about 90%, about 20% to about 60% or about
10% to about 30% by weight of the oral compositions. This amount of
water includes the free water which is added plus that amount which
is introduced with other materials such as with sorbitol or any
components of the invention.
Humectants
[0102] Within certain embodiments of the oral compositions, it is
also desirable to incorporate a humectant to prevent the
composition from hardening upon exposure to air. Certain humectants
can also impart desirable sweetness or flavor to dentifrice
compositions. The humectant, on a pure humectant basis, generally
includes about 15% to about 70% in one embodiment or about 30% to
about 65% in another embodiment by weight of the dentifrice
composition.
[0103] Suitable humectants include edible polyhydric alcohols such
as glycerine, sorbitol, xylitol, propylene glycol as well as other
polyols and mixtures of these humectants. Mixtures of glycerine and
sorbitol may be used in certain embodiments as the humectant
component of the toothpaste compositions herein.
[0104] In addition to the above described components, the
embodiments of this invention can contain a variety of optional
dentifrice ingredients some of which are described below. Optional
ingredients include, for example, but are not limited to,
adhesives, sudsing agents, flavoring agents, sweetening agents,
additional antiplaque agents, abrasives, and coloring agents. These
and other optional components are further described in U.S. Pat.
No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458 to Agricola et
al. and U.S. Pat. No. 3,937,807, to Haefele, all being incorporated
herein by reference.
Methods of Manufacture
[0105] The compositions of the present invention can be made using
methods which are common in the oral product area.
[0106] In one illustrative embodiment, the Salts are made by
neutralizing arginine in a gel phase with the conjugate acid and
mixing to form Premix 1, adjusting the pH to the desired level, and
then combining with the other ingredients. Actives such as, for
example, vitamins, CPC, fluoride, abrasives, and any other desired
active ingredients are added to Premix 1 and mixed to form Premix
2. Where the final product is a toothpaste, a toothpaste base, for
example, dicalcium phosphate or silica, is added to Premix 2 and
mixed. The final slurry is formed into an oral care product.
Composition Use
[0107] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0108] The compositions and methods according to the invention are
useful to a method to protect the teeth by facilitating repair and
remineralization, in particular to reduce or inhibit formation of
dental caries, reduce or inhibit demineralization and promote
remineralization of the teeth, reduce hypersensitivity of the
teeth, and reduce, repair or inhibit early enamel lesions, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electronic caries monitor (ECM).
[0109] Quantitative Light-induced Fluorescence is a visible light
fluorescence that can detect early lesions and longitudinally
monitor the progression or regression. Normal teeth fluoresce in
visible light; demineralized teeth do not or do so only to a lesser
degree. The area of demineralization can be quantified and its
progress monitored. Blue laser light is used to make the teeth auto
fluoresce. Areas that have lost mineral have lower fluorescence and
appear darker in comparison to a sound tooth surface. Software is
used to quantify the fluorescence from a white spot or the
area/volume associated with the lesion. Generally, subjects with
existing white spot lesions are recruited as panelists. The
measurements are performed in vivo with real teeth. The lesion
area/volume is measured at the beginning of the clinical. The
reduction (improvement) in lesion area/volume is measured at the
end of 6 months of product use. The data is often reported as a
percent improvement versus baseline.
[0110] Electrical Caries Monitoring is a technique used to measure
mineral content of the tooth based on electrical resistance.
Electrical conductance measurement exploits the fact that the
fluid-filled tubules exposed upon demineralization and erosion of
the enamel conduct electricity. As a tooth loses mineral, it
becomes less resistive to electrical current due to increased
porosity. An increase in the conductance of the patient's teeth
therefore may indicate demineralization. Generally, studies are
conducted of root surfaces with an existing lesion. The
measurements are performed in vivo with real teeth. Changes in
electrical resistance before and after 6 month treatments are made.
In addition, a classical caries score for root surfaces is made
using a tactile probe. The hardness is classified on a three point
scale: hard, leathery or soft. In this type of study, typically the
results are reported as electrical resistance (higher number is
better) for the ECM measurements and an improvement in hardness of
the lesion based on the tactile probe score.
[0111] The Compositions of the invention are thus useful in a
method to reduce early lesions of the enamel (as measured by QLF or
ECM) relative to a composition lacking effective amounts of
fluorine and/or arginine.
[0112] The Compositions of the invention are additionally useful in
methods to reduce harmful bacteria in the oral cavity, for example
methods to reduce or inhibit gingivitis, reduce levels of acid
producing bacteria, to increase relative levels of arginolytic
bacteria, inhibit microbial biofilm formation in the oral cavity,
raise and/or maintain plaque pH at levels of at least pH about 5.5
following sugar challenge, reduce plaque accumulation, and/or clean
the teeth and oral cavity.
[0113] Finally, by increasing the pH in the mouth and discouraging
pathogenic bacteria, the Compositions of the Invention are useful
to promote healing of sores or cuts in the mouth.
[0114] The compositions and methods according to the invention can
be incorporated into oral compositions for the care of the mouth
and teeth such as toothpastes, transparent pastes, gels, mouth
rinses, sprays and chewing gum.
[0115] Enhancing oral health also provides benefits in systemic
health, as the oral tissues can be gateways for systemic
infections. Good oral health is associated with systemic health,
including cardiovascular health. The compositions and methods of
the invention provide particular benefits because basic amino
acids, especially arginine, are sources of nitrogen which supply NO
synthesis pathways and thus enhance microcirculation in the oral
tissues. Providing a less acidic oral environment is also helpful
in reducing gastric distress and creates an environment less
favorable to Heliobacter, which is associated with gastric ulcers.
Arginine in particular is required for high expression of specific
immune cell receptors, for example T-cell receptors, so that
arginine can enhance an effective immune response. The compositions
and methods of the invention are thus useful to enhance systemic
health, including cardiovascular health.
[0116] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
* * * * *